Previous studies have shown potentially higher exposure to fluticasone furoate in Japanese subjects compared with Caucasian subjects. The reasons for these potential differences are unclear. Therefore this study is being done to look at and compare how fluticasone furoate is processed by the body in healthy Caucasian, Japanese, Korean and Chinese subjects after inhaled and intravenous administration. The data obtained will be used to help in the clinical development of the drug in Japanese and other East Asian populations.
Corticosteroids are a highly effective anti-inflammatory therapy in allergic conditions such as asthma and rhinitis. Fluticasone Furoate (FF) is a novel corticosteroid with potent glucocorticoid activity similar to fluticasone propionate and mometasone furoate. Phase II studies have shown FF to be an effective once daily inhaled steroid for asthma and it is being developed as a potential steroid component in a once daily combination with GW642444M, for once-daily administration for the maintenance treatment of asthma and COPD. FF is approved worldwide (including the US, EU and Japan) as an intranasal steroid for the treatment of allergic rhinitis (VERAMYST™ /AVAMYS™ /ALLERMIST™). Previous inter-study comparisons have indicated potentially higher systemic exposure to FF in Japanese subjects compared with treatment groups that recruited predominantly Caucasian subjects. The reasons for these potential differences are unclear. This study is being performed to evaluate and directly compare the PK and systemic PD effects of FF in healthy Caucasian, Japanese, Korean and Chinese subjects when delivered from the novel dry powder inhaler and intravenously. The data obtained will be used to facilitate clinical development of the FF/GW642444 combination in Japanese and other East Asian populations.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
80
Seven inhaled doses of 200mcg FF given once daily in the morning (Part A; Days 1-7) followed by seven inhaled doses of 800mcg FF given once daily in the morning (Part B; Day 1 and Days 3-8, i.e. no dose on Day 2). A single intravenous dose of 250mcg FF given over 20 minutes (Day 1).
GSK Investigational Site
Randwick, New South Wales, Australia
FF Pharmacokinetic parameters: AUC, Cmax, t1/2, tmax for inhaled and intravenous treatments. Volume of distribution (V) and plasma clearance (CL) for intravenous FF
Time frame: up to 72hr PK sampling periods profiles on 4 separate occasions over a total period of approximately 4-5 weeks
Pharmacokinetic parameters MRT for both inhaled and intravenous treatments; MAT, AUC(0-t) for 200mcg dose,observed accumulation (Ro) and absolute bioavailability for inhaled treatment
Time frame: up to 72hr PK sampling periods profiles on 4 separate occasions over a total period of approximately 4-5 weeks
Pharmacodynamics; serum cortisol for 200mcg inhaled FF treatment only: 24 hour weighted mean (on Day -1 and Day 7)
Time frame: Two 24 hour sampling periods approximately 1 week apart
• Ratio of twenty-four hour urine cortisol to 6-beta-hydroxy-cortisol (on Day -1 of first treatment period only). Plasma 4-beta-hydroxy-cholesterol (single sample, on Day -1 of first treatment period only). Measure of baseline CYP3A4 activity
Time frame: One collection period of up to 24 hours
• Vital signs, 12-lead ECG, Clinical laboratory tests, forced expiratory volume in 1 second (FEV1) (at screening), peak expiratory flow rate (PEFR), AEs.
Time frame: Throughout study; approx 10 weeks
Quantity of the total emitted dose (TED), ex-throat dose (ETD) and mass less than 2 micrometer of inhaled FF for each subject, assessed by pharyngometry, inhalation profile, breath hold and lung volume measurements
Time frame: Throughout study from screening to end of treatment periods; approximately 8 weeks
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